
<ArticleTitle>Fatal propionic acidemia in mice lacking <prot>propionyl-CoA carboxylase</prot> and its rescue by postnatal, liver-specific supplementation via a transgene.</ArticleTitle>
<AbstractText>Propionic acidemia (PA) is an inborn error of metabolism caused by the genetic deficiency of <prot>propionyl-CoA carboxylase</prot> (<prot>PCC</prot>). By disrupting the alpha-subunit gene of <prot>PCC</prot>, we created a mouse model of PA (PCCA(-/-)), which died in 24-36 h after birth due to accelerated ketoacidosis. A postnatal, liver-specific <prot>PCC</prot> expression via a transgene in a far lower level than that in wild-type liver, allowed PCCA(-/-) mice to survive the newborn and early infant periods, preventing a lethal fit of ketoacidosis (SAP(+)PCCA(-/-) mice). Interestingly, SAP(+)PCCA(-/-) mice, in which the transgene expression increased after the late infant period, continued to grow normally while mice harboring a persistent low level of <prot>PCC</prot> died in the late infant period due to severe ketoacidosis, clearly suggesting the requirement of increased <prot>PCC</prot> supplementation in proportion to the animal growth. Based on these results, we propose a two-step strategy to achieve an efficient PA prevention in human patients: a partial <prot>PCC</prot> supplementation in the liver during the newborn and early infant periods, followed by a larger amount of supplementation in the late infant period.</AbstractText>
